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(11) | EP 0 136 147 A2 |
| (12) | EUROPEAN PATENT APPLICATION |
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| (54) | N-(Alpha-haloacyl)-N-hydrocarbyl carbamoyl halides and process for preparation |
| (57) N-(alpha-haloacyl)-N-hydrocarbyl carbamoyl halides and a process for their preparation
are provided. The compounds are useful as intermediates in the preparation of insecticides
and have the general formula:
wherein: R represents alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, of up to 18 carbon atoms, and wherein such groups may be optionally substituted with halogen, cyano, nitro, or alkoxy, alkylthio, alkyl, alkenyl, alkynyl or cycloalkyl, groups of up to 12 carbon atoms; R' represents hydrogen, halo, or alkyl, of up to 12 carbon atoms; and X represents Cl or F and Y represent Cl, F or Br. |
[0001] This invention relates in general to N-(alpha-haloacyl)-N-hydrocarbylcarbamoyl halides and to a process for their preparation. In one aspect, this invention relates to carbamoyl halides which are useful as intermediates in the preparation of pesticides.
[0002] Prior to the present invention few literature references'were available which disclosed carbamoyl halides. For example, GB-A-1,226,450 which was published March 31, 1971 disclosed certain N-substituted N-acylcarbamic acid halides of the formula:
wherein R' represents alkyl, aralkyl, alkenyl aralkenyl. cycloalkyl, heterocyclic or aryl radicals. R2 represents alkyl or alkynyl radicals and X represents halogen. The reference further indicates that R1 and R2 may be optionally substituted with certain other groups. However. compounds wherein R1 is an alpha-haloalkyl were not disclosed. published May 26, 1971 discloses compounds of the formula:
wherein R represents a hydrogen atom or alkyl. and R4 represents an optionally substituted alkanoyl group particularly, acetyl, chloroacetyl, dichloroacetyl and trichloroacetyl.
[0003] In its broad aspect the invention relates to N-(alpha-haloacyl)-N-hydrocarbylcarbamoyl halides, processes for their preparation and use of the compounds as intermediates for the preparation of pesticides. The carbamoyl halides can be represented by the following formula I:
wherein R, R1. X and Y are as hereinafter described.
[0004] As indicated above, the carbamoyl halides of this invention are conveniently represented by the formula:
wherein:
R represents alkyl, alkenyl, alkynyl. cycloalkyl, cycloalkenyl, aralkyl, of up to 18 carbon atoms, and wherein such groups may be optionally substituted with halogen, cyano, nitro or alkoxy, alkylthio, alkyl, alkenyl, alkynyl or cycloalkyl groups of up to 12 carbon atoms:
R represents hydrogen, halo, or alkyl. R1 preferably contains up to 18 carbon atoms and can optionally be substituted with halogen, cyano, nitro or alkoxyl, alkylthio, alkenyl, alkynyl or cycloalkyl groups of up to 12 carbon atoms. X represents Cl or F and Y represents Cl. F or Br.
[0005] Illustrative carbamoyl halides which are encompassed by the aforementioned formula are illustrated by, but not limited to, the following: N-Chloroacetyl-N-ethylcarbamoyl chloride. N-(n-Butyl)-N-chloroacetylcarbamoyl chloride, N-Chloroacetyl-N-(n-pentyl)carbamoyl chloride. N-Chloroacetyl-N-(n-hexyl)carbamoyl chloride, N-Chloroacetyl-N-isopropylcarbamoyl chloride, N-Chloroacetyl-N-isobutylcarbamoyl chloride, N-Chloroacetyl-N-isoamylcarbamoyl chloride. N-Chloroacetyl-N-(2-propen-1-yl)carbamoyl chloride, N-Chloroacetyl-N-(2-propyn-1-yl)carbamoyl chloride. N-Chloroacetyl-N-(2-cyanoethyl)carbamoyl chloride, N-Chloroacetyl-N-(2-chloroethyl)carbamoyl chloride. N-Chloroacetyl-N-(2-methoxyethyl)carbamoyl chloride, N-Chloroacetyl-N-(2-methylthioethyl)carbamoyl chloride, N-Chloroacetyl-N-cyanomethyl carbamoyl chloride, N-Chloroacetyl-N-cyclopropyl carbamoyl chloride, N-Chloroacetyl-N-cyclohexylcarbamoyl chloride, N-Chloroacetyl-N-propyl carbamoyl fluoride, N-bromoacetyl-N-butyl carbamoyl fluoride, N-(2-Chlorobutyryl)-N-methylcarbamoyl fluoride, N-(2-Chlorohexanoyl)-N-methylcarbamoyl chloride, and N-(2-fluoropropionyl)-N-methylcarbamoyl chloride.
[0006] The carbamoyl halides of this invention are conveniently prepared by the reaction of alpha-haloacyl chlorides with suitable isocyanates according to the scheme set forth below:
wherein R, R and Y are as previously indicated.
[0007] Freshly activated zinc chloride supported on silica gel is the preferred catalyst for this reaction. Freshly activated zinc chloride in combination with other supports such as clay, sand, anhydrous magnesium sulfate are also effective catalysts. However, various other Lewis acid catalysts such as SnCl4, SnCl2, CuCl. CuBr, HgCl2, ZnBr2, SbCl5, and TiCl may also be used in a suitably activated form or in combination with inert supporting materials or heterogeneous reaction catalyzing materials such as crown ethers and quaternary ammonium salts.
[0008] Suitable reaction temperatures fall in the range from -30 to +150°C, however, temperatures from 0 to 75°C are preferred. The reaction can be carried out in absence of a solvent, however inert solvents such as hydrocarbons, chlorinated hydrocarbons, ethers, nitriles, sulfones and ketones may be used. The reaction can be carried out under atmospheric pressure but lower or higher pressures may also be used.
[0009] Using reagent grade anhydrous zinc chloride catalyst, as used to prepare the prior art (GB-A- 1226450) compounds, chloroacetyl chloride and methyl isocyanate do not afford the desired product, whereas y-chlorobutyryl chloride smoothly reacts with methyl isocyanate to yield the corresponding N-(y-chlorobutyryl)-N-methylcarbamoyl chloride.
[0010] The carbamoyl fluorides of this invention are conveniently prepared from the corresponding carbamoyl chlorides (I) by an exchange reaction. For example, N-chloroacetyl-N-methylcarbamoyl fluoride is prepared from N-chloroacetyl-N-methylcarbamoyl chloride by reacting the chloride with anhydrous potassium fluoride as indicated in Example 6. Other metal fluorides, such as the alkali and alkaline earth fluorides can also be used to effect the exchange. For example sodium fluoride or cesium fluoride can equally as well be employed.
[0011] As hereinbefore indicated the compounds of this invention are useful as intermediates in the preparation of pesticides and other related compounds. It has been observed that the N-(alpha-haloacyl)-N-hydrocarbylcarbamoyl halides of the present invention differ markedly in the reactivity from the prior art compounds disclosed in the aforementioned GB-A- 1,226,450. This is believed to be due in part to the unique alpha-position of the halogen atom as opposed to the beta-or gamma halo position of the known compounds. In addition to the highly reactive carbamoyl halide function, the halogen of the alpha-haloacyl function is thus sufficiently reactive so that it can be subsequently substituted by various nucleophiles. For example, the compounds of this invention react with phenols and oximes to yield the corresponding N-(alpha-haloacyl)-N-hydrocarbyl carbamates. These carbamates can be further reacted with various nucleophiles to yield pesticidally or otherwise biologically active derivatives.
[0012] For example, the reaction of a carbamoyl halide of this invention affords the corresponding N-haloacylcarbamate in high yield:
[0013] Further reaction of the carbamate with trimethyl amine gives the corresponding amine salt which has excellent pesticidal properties:
[0014] Similarly, the carbamoyl halide can be reacted with an oxime in accordance with the following equation:
[0015] In contrast, it was noted that a similar reaction of the prior art (GB-A- 1,226,450) compounds (XIII) with (X).lead to less active or inactive materials (XIVa) and (XIVb) as set forth in Table I.
[0016] The following examples illustrate the best mode presently contemplated for the practice of this invention.
Example 1
Preparation of Representative Catalysts Suitable for the Preparation of N-(alpha-haloacyl)-N-hydrocarbyl- carbamoyl halides
[0017] Catalyst A: 10g of reagent grade anhydrous zinc chloride and 10g. of silica gel were ground together to give an intimate mixture. This mixture was heated in an open beaker in a furnace at about 350°C for about 1 hour to activate and spread the zinc chloride uniformly over the surface of the silica gel particles. The material was then cooled in a desiccator and directly used for the reaction. Zinc chloride and silica gel may be used in various other proportions, however, a minimum proportion of silica gel which can prevent the formation of lumps of the catalyst is preferred.
[0018] Catalyst B: 10g. of silica gel was treated with a solution of lOg of anhydrous zinc chloride in 25 c.c. distilled water. Water was stripped off under reduced pressure at about 80°C. The resultant powder was then heated in an open beaker in a furnace at 350°C for about 1 hour, cooled in a desiccator and directly used for the reaction.
[0019] Catalyst C: Reagent grade anhydrous zinc chloride was fused in an open beaker on flame or in a furnace at about 350°C. The fused liquid was spread out over a smooth surface like a watch glass or a tin lid and cooled in a desiccator over fused calcium chloride. After cooling, the zinc chloride was scraped off and the flakes were ground to a fine powder under dry nitrogen.
[0020] Catalyst D: Reagent grade anhydrous zinc chloride was fused and cooled as in the case of catalyst C. Silica gel was also activated at 350°C and cooled similarly. Equal quantities of the activated zinc chloride and silica gel were ground together to fine powder. The ratios of zinc chloride and silica gel may be varied from 0.1 percent to.80 percent of zinc chloride mixed with silica gel.
Example 2
Preparation of N-Chloroacetyl-N-methylcarbamoyl chloride
[0021] A mixture of 20.0g. of Catalyst A and 56.5g. (0.50m) of chloroacetyl chloride was stirred under dry nitrogen. Cooling the reaction flask in an ice bath. 31.5g (0.55m) of methyl isocyanate was added. Stirring was continued and the bath temperature was raised slowly to 50°C under reflux. The reaction was continued at 50-55°C for about 16 hours and then cooled to room temperature. The unreacted chloroacetyl chloride and methyl isocyanate were stripped off at room temperature under 0.25mm pressure., The residual solid was extracted with dichloromethane and then the solvent was stripped off under reduced pressure to afford 60.0g (yield 70.5%) of
N-Chloroacetyl-N-methylcarbamoyl chloride. M.p. 67-69°C.
[0022] NMR (CDCl3) δ 4.65 (s,2H) and 3.50 (s,3H). 1.R. (CHCl3) ν1765 and 1740 cm-1 Calcd for C4H5Cl2NO2:
C. 28.26: H, 2.96: N. 8.24. Found: C. 28.40: H, 2.97; N, 8.12
[0023] The above reaction when carried out in a closed reactor under autogeneous pressure at 0°C to 30°C and worked up similarly, gave the product in 80.5% yield.
[0024] Use of 11.0g. of the Catalyst C or 22.0g. of the Catalyst D in the above reaction and purification of the product by sublimation or distillation under reduced pressure resulted in each case in about 53 percent yield of the product.
Example 3
Preparation of N-Chloroacetyl-N-propylcarbamoyl chloride
[0025] n-Propyl isocyanate was reacted with chloracetyl chloride in presence of Catalyst A, similar to Example 2, to afford N-chloroacetyl-N-(n-propyl)-carbamoyl chloride in 78% yield. M.p. 40-44°C. NMR(CDC1 ) δ 4.65(s,2H), 3.90(t, 2H), 1.70 (m,2H) & 0.90(t,3H) 1R(CDCl3) u1755 & 1735 cm-1
Example 4
Preparation of N-( α-Chloropropionyl)-N-methyl- carbamoyl chloride
[0026] A mixture of 2.0g. of the Catalyst C and 28.2g. (0.25m) of a-Chloropropionyl chloride was stirred under nitrogen at 0°C and 14.5g. (0.25m) of methylisocyanate was added dropwise. The mixture was stirred at room temperature for 16 hours and then refluxed for about 12 hours, Cooled to room temperature and the liquid was decanted from the solid catalyst. Unreacted methyl isocyanate and α-chloropropionyl chloride were stripped off under reduced pressure. The residual product was purified by distillation at 69-76°C under about 0.4-0.5mm pressure to afford 8.5g. (23%) of the title compound (a low melting solid). NMR(CC14) δ 5.25(q, 1H), 3.40(s,3H) and 1.65(d,3H). 1R (Neat) vl770 and 1735 cm-1
Example 5
[0028] A mixture of 5.0g. of the Catalyst C and 30.0g (0.19m) of bromoacetyl chloride was stirred at 0°C under nitrogen and 13.0g (0.23m) of methyl isocyanate was added dropwise. Stirring was continued and the temperature was slowly raised to 50°C under reflux during 5 hours. The reaction was almost complete and the mixture was solidified. The product was purified by distillation under reduced pressure to afford 23.0g (yield 56.0%) of N-bromoacetyl-N-methylcarbamoyl chloride. B.p. 90-95°C/3-5mm. NMR (CC14) δ 4.50 (s,2H) and 3.50 (s,3H). 1R(CHCl3) ν 1750 and 1730 cm-1.
Example 6
Preparation of N-Chloroacetyl-N-methylcarbamoyl fluoride
[0029] A mixture of 10.Og of N-Chloroacetyl-N-methylcarbamoyl chloride, 3.8g of anhydrous potassium fluoride and 0.5g of 18-crown-6 in 50cc of dichloromethane was stirred at room temperature under nitrogen for about 16 hours. The liquid was decanted and the residue was extracted with 50cc dichlormethane. The dichloromethane layers were combined and the solvent stripped off to afford 9.0g. (yield 100%) of N-chloroacetyl-N-methylcarbamoyl fluoride. The product was further purified by distillation under reduced pressure. B.p. 59°C/0.2mm.
NMR(CDC1 ) δ 4.70(s,2H) and 3.30(d,3H, J 2Hz) 1R (CHCl3) ν1820 and 1735 cm-1.
[0030] A comparision of an oxime derivative of the compounds of this invention was evaluated to determine its pesticidal activity against certain mites and insects including the Bean Aphid, Southern Army Worm. Mexican Bean Beetle and house fly. The oxime derivative was also compared with typical derivative of this oxime as disclosed in GB-A- 1,226,450.
[0031] Suspensions of the test compounds were prepared by dissolving one gram of compound in 50 milliliters of acetone in which had been dissolved 0.1 gram (10 percent of the weight of compound) of an alkylphenoxy polyethoxyethanol surfactant, as an emulsifying or dispersing agent. The resulting solution was mixed into 150 milliliters of water to give roughly 200 milliliters of a suspension containing the compound in finely divided form. The thus-prepared stock suspension contained 0.5 percent by weight of compound.
[0032] Certain of the test compounds were also prepared by dissolving 375 mg of compound in 7.5 ml of dimethylformamide. Fifteen ml of acetone containing 37.5 mg (10 percent of the weight of test compound) of an alkylphenoxy polyethoxyethanol surfactant, as a wetting/emulsifying/dispersing agent was added to the dimethylformamide solution. Fifty-two and a half ml of water was mixed into the dimethylformamide-acetone mixture to give roughly 75 ml of a suspension containing the compound in solution or in finely divided form. The thus prepared stock suspension contained 0.5 percent by weight of compound. The test concentrations in parts per million by weight employed in the tests described hereinbelow were obtained by appropriate dilutions of the stock suspension with water. The test procedures were as follows:
Bean Aphid Foliage Spray Test
[0033] Adults and nymphal stages of the bean aphid (Aphis fabae Scop.) reared on potted dwarf nasturtrium plants at 68°-70°F. and 50 ± 5 percent relative humidity, constituted the test insects. For testing purposes, the number of aphids per pot was standardized to 100-150 by trimming plants containing excess aphids.
[0034] The test compounds were formulated by diluting the stock suspension with water to give a suspension containing 500 parts of test compound per million parts of final formulation.
[0035] The potted plants (one pot per compound tested) infested with 100-150 aphids were placed on a revolving turntable and sprayed with 100-110 milliliters of test compound formulation by use of a DeVilbiss spray gun set at 40 psig air pressure. This application, which lasted 25 seconds, was sufficient to wet the plants to run-off. As a control, 100-110 milliliters of a water-acetone-emulsifier solution containing no test compound were also sprayed on infested plants. After spraying, the pots were placed on their sides on a sheet of white standard mimeograph paper which had been previously ruled to facilitate counting. Temperature and humidity in the test room during the 24 hour holding period were 68°-70°F. and 50 ; 5 percent, respectively. Aphids which fell onto the paper and were unable to remain standing after being uprighted were considered dead. Aphids remaining on the plants were observed closely for movement and those which were unable to move the length of the body upon stimulation by prodding were considered dead. Percent mortality was recorded for various concentration levels.
Southern Army-worm Leaf Spray Bait Test
[0036] Larvae of the southern armyworm (Spodeptere eridania, (Cram.)), reared on Tendergreen bean plants at a temperature of 80°+5° F. and a relative humidity of 50±5 percent, constituted the test insects.
[0037] The test compounds were formulated by diluting the stock suspension with water to give a suspension containing 500 parts of test compound per million parts of final formulation. Potted Tendergreen bean plants of standard height and age were placed on a revolving turntable and sprayed with 100-110 milliliters of test compound formulation by use of a DeVilbiss spray gun set at 40 psig air pressure. This application, which lasted 25 seconds, was sufficient to wet plants to run-off. As a control, 100-110 milliliters of a water-acetone-emulsifier solution containing no test compound were also sprayed on infested plants. When dry, the paired leaves were separated and each one was placed in a 9 centimeter Petri dish lined with moistened filter paper. Five randomly selected larvae were introduced into each dish and the dishes were closed. The closed dishes were labeled and held at 80°-85° F. for five days. Although the larvae could easily consume the whole leaf within twenty-four hours, no more food was added. Larvae which were unable to move the length of the body, even upon stimulation by prodding, were considered dead. Percent mortality was recorded for various concentration levels.
Mexican Bean Beetle Leaf Spray Test
[0038] Fourth instar larvae of the Mexican bean beetle (Epilachna varivestis, Muls.), reared on Tendergreen bean plants at a temperature of 80°±5° F. and 50+5 percent relative humidity, were the test insects.
[0039] For certain of the tests second instar larvae (weighing about 6 mg) of the Mexican bean beetle (Epilachna varvestis. Muls). reared on Seiva Pole lima bean plants at a temperature of 80° ± 5°F and 5 ± 5 percent relative humidity, were the test insects.
[0040] The test compounds were formulated by diluting the stock suspension with water to give a suspension containing 500 parts of test compound per million parts of final formulation. Potted Tendergreen bean plants of standard height and age were placed on a revolving turntable and sprayed with 100-110 milliliters of test compound formulation by use of a DeVilbiss spray gun set at 40 psig air pressure. This application, which lasted 25 seconds, was sufficient to wet plants to run-off. As a control, 100-110 milliliters of a water-acetone-emulsifier solution containing no test compound were also sprayed on infested plants. When dry, the paired leaves were separated and each was placed in a 9 centimeter Petri dish lined with moistened filter paper. Five randomly selected larvae were introduced into each dish, and the dishes were closed. The closed dishes were labeled and held at a temperature of 80°±5° F., for five days. Although the larvae could easily consume the leaf within 24 to 48 hours, no more food was added. Larvae which were unable to move the length of the body, even upon stimulation, were considered dead.
Fly Bait Test
[0041] Four to six day old adult house flies (Musca domestica, L.), reared according to the specifications of the Chemical Specialties Manufacturing Association (Blue Book, McNair-Dorland Co:, N.Y. 1954: pages 243-244, 261) under controlled conditions of 80° ± 5°F. and 50 ± 5 percent relative humidity, were the test insects. The flies were immobilized by anesthetizing with carbon dioxide and twenty-five immobilized individuals, males and females, were transferred to a cage consisting of a standard food strainer about five inches in diameter which was inverted over a wrapping-paper-covered surface. The test compounds were formulated by diluting the stock suspension with a 10 percent (by weight) sugar solution to give a suspension containing 500 parts of test compound per million parts of final formulation, by weight. Ten milliliters of the test formulation were added to a souffle cup containing a one-inch square of an absorbent cotton pad. This bait cup was introduced and centered on the blotting paper under the food strainer prior to admitting the anesthetized flies. The caged flies were allowed to feed on the bait for twenty-four hours, at a temperature of 80° ± 5°F. and a relative humidity of 50 ± 5 percent. Flies which showed no sign of movement on prodding were considered dead.
1. A carbamoyl halide compound of the general formula:
wherein:
wherein:
R represents alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, of up to 18 carbon atoms, and wherein such groups may be optionally substituted with halogen, cyano, nitro, or alkoxy, alkylthio, alkyl, alkenyl, alkynyl or cycloalkyl groups of up to 12 carbon atoms; R1 represents hydrogen, halo, or alkyl, of up to 12 carbon atoms; and X represents Cl or F and Y represent Cl, F or Br.
2. A compound as claimed in claim 1 wherein X and Y both represent chloro groups.
3. A compound as claimed in claim 1 wherein X represents a chloro and Y represents
a bromo group.
4. A compound as claimed in claim 1 wherein X represents a fluoro and Y represents
a chloro group.
5. A compound as claimed in any one of the preceding claims wherein R1 represents hydrogen.
6. A compound as claimed in any one of claims 1 to 4 wherein R and R both represent
alkyl.
7. N-chloroacetyl-N-methylcarbamoyl chloride.
8. N-chloroacetyl-N-propylcarbamoyl chloride.
9. N-(alpha-chloro-propionyl)-N-methylcarbomyl chloride.
10. N-bromoacetyl-N-methylcarbamoyl chloride.
11. N-chloroacetyl-N-methylcarbamoyl fluoride.
12. A process for the preparation of a carbamoyl halide as claimed in claim 1 wherein
X is Cl which comprise reaction of an isocyanate of the formula:
wherein R is as defined in Claim 1 with an alpha-haloacyl halide of the formula:
wherein R1 and Y are as defined in claim 1
wherein R is as defined in Claim 1 with an alpha-haloacyl halide of the formula:
wherein R1 and Y are as defined in claim 1
13. A process for the preparation of a carbamoyl halide as claimed in claim 1 wherein
X is F which comprises reacting a carbamoyl halide of the formula:
wherein R, R1 and Y are as defined in claim 1 with a metal fluoride.
wherein R, R1 and Y are as defined in claim 1 with a metal fluoride.
14. A process as claimed in claim 12 wherein the reaction is conducted in the presence
of a catalyst which is activated zinc chloride.
15. A process as claimed in claim 14 wherein the catalyst is contained on a silica
gel support.
16. A process as claimed in any one of claims 12, 14 or 15 wherein the reaction is
conducted at a temperature of from -30 to 150°C.
17. A pesticidal carbamate or oxime derivative of a carbamoyl halide compound as claimed
in claim 1 when formed from such compound.